Using genes to facilitate the endogenous repair and regeneration of orthopaedic tissues

Traditional tissue engineering approaches to the restoration of orthopaedic tissues promise to be expensive and not well suited to treating large numbers of patients. Advances in gene transfer technology offer the prospect of developing expedited techniques in which all manipulations can be performed percutaneously or in a single operation. This rests on the ability of gene delivery to provoke the sustained synthesis of relevant gene products in situ without further intervention. Regulated gene expression is also possible, but its urgency is reduced by our ignorance of exactly what levels and periods of expression are needed for specific gene products. This review describes various strategies by which gene therapy can be used to expedite the repair and regeneration of orthopaedic tissues. Strategies include the direct injection of vectors into sites of injury, the use of genetically modified, allogeneic cell lines and the intra-operative harvest of autologous tissues that are quickly transduced and returned to the body, either intact or following rapid cell isolation. Data obtained from pre-clinical experiments in animal models have provided much encouragement that such approaches may eventually find clinical application in human and veterinary medicine.